Daily dose of oral edaravone for ALS nonsuperior to staggered regimen at 48 weeks

Key takeaways:

• Both edavarone dosing regimens produced similar safety and efficacy results.
• Based on study data, a staggered edaravone regimen is most appropriate for those with ALS.

For individuals with ALS, a daily dosing regimen of oral edaravone was nonsuperior to an FDA-approved staggered regimen of the drug plus placebo, according to a poster presented at AANEM.

“Radicava ORS oral suspension was FDA approved for use in patients with ALS in May 2022, based on bioequivalence and long-term safety studies,” Alejandro Salah, MD, PhD, MBA, MHA, BCMAS, study co-author and medical director of medical affairs – ALS at Mitsubishi Tanabe Pharma America, and colleagues wrote.

Salah and colleagues compared the safety, efficacy and tolerability of two daily doses of edaravone (Radicava ORS, Mitsubishi Tanabe Pharma) in patients with ALS.

They conducted a phase 3b multicenter, double-blind, randomized, parallel-group clinical trial that included 383 adults (64% men; mean age 58.9 years) with either probable or definite ALS, a baseline score of 2 or higher on the ALS Functional Rating Scale-Revised (ALSFRS-R) and appearance of initial ALS symptoms 2 years or less from the time written consent was given.

Following an 8-week screening period, participants were randomly assigned on a 1:1 basis ahead of a 48-week treatment interval to receive either a steady once-daily regimen of 105 mg edaravone or an on/off regimen of 105 mg edaravone for 14 days, placebo for 14 days, 105 mg edaravone for 10 days then placebo for 18 days. A safety follow-up interval of 2 weeks preceded the end of the study.

The primary efficacy endpoint was score on the Combined Assessment of Function and Survival (CAFS) at week 48, with primary safety endpoints including total number of adverse events including treatment-emergent adverse events and adverse drug-related reactions.

A total of 246 patients completed the 48-week treatment period and 95 completed the 2-week safety follow up, while 138 individuals elected to discontinue treatment.

According to the results, no significant difference was recorded among the treatment groups with respect to CAFS by week 48, while both dosing regimens led to similar changes in ALSFRS-R from baseline to end of the double-blind treatment interval.

The researchers also found no superiority between the treatment groups on any secondary efficacy endpoints.

At least one TEAE was recorded in 165 individuals in the once-daily treatment group and 178 were recorded in the staggered dosing regimen group, with serious TEAEs reported in 52 patients in the once-daily edaravone group and 55 in the staggered treatment cohort.

Data further show 47 patients in the once-daily group and 32 in the staggered group experienced at least one TEAE, with headache the most common complaint among both groups.

"These findings reflect our unwavering dedication to deepening our understanding of ALS and exploring treatment approaches that could make a meaningful difference for people living with ALS,” Gustavo A. Suarez Zambrano, MD, vice president of medical affairs at Mitsubishi Tanabe Pharma America, said in a release related to the study.

Reference:

Mitsubishi Tanabe Pharma America to showcase ALS research at 2024 AANEM Annual Meeting. https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-to-showcase-als-research-at-2024-aanem-annual-meeting-302275445.html. Published Oct. 15, 2024. Accessed Nov. 14, 2024.